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Critical Reviews™ in Eukaryotic Gene Expression

Impact factor: 1.660

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2016015920
pages 115-132

Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise

Loreana Sanches Silveira
Immunometabolism Research Group, Institute of Biomedical Sciences, Department of Cell Biology and Development, University of Sao Paulo, Av. Prof Lineu Prestes, 1524, 05508-000 Sao Paulo, SP, Brazil; Exercise and Immunometabolism Research Group, Department of Physical Education, University of the State of Sao Paulo, Rua Roberto Simonsen, 305, 19060-900 Presidente Prudente, SP, Brazil
Barbara de Moura Mello Antunes
Exercise and Immunometabolism Research Group, Department of Physical Education, University of the State of Sao Paulo, Rua Roberto Simonsen, 305, 19060-900 Presidente Prudente, SP, Brazil
Andre Luis Araujo Minari
Psychobiology Department, Federal University of Sao Paulo, UNIFESP, Sao Paulo, Brazil
Ronaldo Vagner Thomatieli dos Santos
Psychobiology Department, Federal University of Sao Paulo, UNIFESP, Sao Paulo, Brazil; Bioscience Department, Campus Baixada Santista, Federal University of Sao Paulo, UNIFESP, Santos, Brazil
José Cesar Rosa Neto
Immunometabolism Research Group, Department of Cell Biology and Development − Institute of Biomedical Sciences I − University of Sao Paulo (USP), Sao Paulo, Brazil
Fábio Santos Lira
Immunometabolism Research Group, Department of Cell Biology and Development − Institute of Biomedical Sciences I − University of Sao Paulo (USP), Sao Paulo, Brazil

ABSTRACT

Macrophages are cells of the innate immune response that trigger inflammation resolution. The phenotype of "classically activated macrophages" (M1) has anti-tumoricidal and anti-bactericidal activities. On the other hand, "alternatively activated macrophages" (M2) are involved in tissue remodeling and immunomodulatory functions. The change in the polarization of macrophages varies according to the diversity of cytokines present in the microenvironment or by the stimuli of an antigen. It involves such factors as interferon-regulatory factors, peroxisome proliferator-activated receptors (PPARs), hypoxia-inducible factors (HIFs), and signal transducers and activators of transcription (STATs). Switching the phenotype of macrophages can help attenuate the development of an inflammatory disease. Exercise can promote alterations in the number of innate immune cells and stimulates phagocytic function. Chronic exercise seems to inhibit macrophage infiltration into adipose tissue by attenuating the expression of F4/80 mRNA. Furthermore, exercise may also increase the expression of M2 markers and reduce TNF-α and TLR4 mRNA expression, which activates the inflammatory pathway of NF-κB. Chronic exercise reduces β2-adrenergic receptors in monocytes and macrophages by modulating TLR4 signaling as well as suppressing IL-12 production, a stimulator of interferon Y. In this review, we discuss macrophage polarization in metabolic diseases and how exercise can modulate macrophage plasticity.